The radionuclide gallium-67 (Ga-67) is a valuable aid in human tumor detection. Many tumors concentrate Ga67 and can be detected by scanning techniques (1-10). The basis for its concentration in neoplastic tissue is unknown although much basic work has been carried out (11-17). Because of the many analogies between oncogenesis and embryogenesis, we made preliminary studies of the distribution of Ga67 in pregnant animals. These studies showed marked concentration of the isotope in placental and mammary tissues and concomitant lack of uptake in thymus (18). Tumor-bearing rats also show diminished Ga67 uptake in thymus tissues (Hayes, et al., unpublished results). The study of Ga67 localization during embryogenesis may thus prove to be valuable in elucidating the basis for altered Ga67 distribution in oncogenesis. We propose to study the tissue distribution of Ga67 at various stages of embryogenesis in the rat and rabbit. The study of Ga67 distribution in pseudopregnant or hormonally treated, ovariectomized animals will determine the degree to which the alterations of Ga67 distribution in pregnant animals is related to hormone action in the absence of fetal tissue. We plan to isolate the subcellular and molecular species that bind Ga67 in fetal and maternal tissues at various stages of gestation. Antisera prepared against the Ga67 binding fractions isolated from rat placenta will be tested for cross reactivity with Ga67 binding fractions extracted from rat tumors and from normal thymus tissue. We will study the association of Ga67 localization with fetal antigen expression in the hamster in vivo and with human carcino-embryonic antigen in vitro. The relationship between activation of RNA-directed DNA polymerases and Ga67 binding in endometrial tissue will also be studied. Should Ga67 binding by tumor tissue be related to specific fetal protein expression, the clinical usefulness of Ga67 could be increased in that localization or lack thereof would be indicative of the nature of the tumor. Likewise the relationship between gallium-binding moieties in thymus, placental and tumor tissue could provide a new tool to study the host responses to both fetal and neoplastic tissue.